Previous population studies have noted a higher rate of peripheral arterial disease (PAD) in African- Americans (Afr.Amer) compared to non-Hispanic whites (NHW). This excess in Afr-Amer is not explained by higher levels of standard PAD risk factors such as diabetes, cigarette smoking, dyslipidemia, and hypertension. This application has two related specific aims. The first specific aim is to determine if the sharply higher prevalence of PAD in Afr-Amer compared to NHW can be explained in whole or in part by different levels of newer atherogenic, inflammatory, thrombotic, and fibrinolytic risk markers for PAD. The second specific aim is to determine whether the higher PAD rate in Afr. Amer can be explained in whole or in part by differential susceptibility to these newer risk markers; that is, an effect-modification of one or more of these newer risk markers by Afr. Amer. ethnicity. An exploratory specific aim also addresses these two questions in Hispanics and Asians. Both specific aims will be addressed using logistic regression models. PAD cases (n=127) and age and sex-matched controls (n=127) will be drawn from a completed population study in which Afr-Amer showed a significant PAD excess not explained by standard PAD risk factors. Ten newer risk markers will be measured on stored frozen plasma. These risk markers are the atherogenic markers homocysteine and lipoprotein antigen; the inflammatory markers c-reactive protein, fibrinogen, interleukin 6, and tumor necrosis factor alpha; the thrombotic markers von Willebrand factor and prothrombin 1-2; and the fibrinolytic markers fibrin D-dimer and plasmin-anti-plasmin. The first specific aim will be addressed by evaluating the change in the risk for Afr-Amer ethnicity when the newer risk markers are entered into the logistic model containing standard PAD risk factors. The specific second aim will be explored by evaluating interaction terms for effect-modification between Afr-Amer ethnicity and the newer risk markers in the logistic model. This is the first attempt to see if these newer risk markers can explain ethnic differences in PAD. Thus, this application is highly innovative and addresses original hypotheses.